This revised proposal is designed to characterize the regulation of expression of the dentin matrix protein - 1 (DMP-1) gene. DMP-1 is a secreted protein found predominately in dentin, but DMP-1 mRNA is also detected by in situ hybridization in osteoblasts. The hypothesis to be tested is that tissue specificity is due to interactions between transcription factors and gene DNA sequences in the DMP-1 promoter and upstream regions. The specific aims are to (1) characterize and compare DNA sequences for the human and murine DMP-1 genes; (2) determine upstream regions that confer tissue-specific expression using gene transfer of expression vectors into cultured odontoblasts and other cell types; and (3) to determine the importance of methylation in tissue specific expression.